A major difficulty encountered with many organic compounds, particularly those of higher molecular weight and/or those having relatively complicated formulas, such as, pharmaceuticals, is that they are highly insoluble in water. This places significant limitations on the potential uses of these materials. For example, for those organic compounds which are used for industrial purposes, normally, a wide variety of organic solvents can be used. However, such solvents often present problems from the standpoint of cost and/or environmental impact. As a result, normally associated with the use of such organic solvents is the problem of their recovery so as to minimize the cost involved with their use, or their neutralization in the sense that the solvents no longer present an environmental or health hazard to humans or animals.
It is thus desirable that such compounds, rather than being utilized in organic solvents, be dissolved in water as the solvent. However, because of the nature of the organic compounds, it is often impossible to achieve a sufficiently high concentration of the organic material in water to facilitate the particular industrial use or chemical reaction desired.
This is particularly so with organic compounds which are used for agricultural purposes, such as, herbicides, pesticides, and the like. Thus, such compounds are normally applied to the plants and/or the earth in which the plants are growing and the best means of transporting the material into the plant or the earth is through water transport. However, because of the insolubility of many of these compounds, it is necessary to formulate them into emulsions or dispersions, usually in the presence of appropriate surface-activating agents, e.g., surfactants, and the like. The formulation of such emulsions increases the expense and manpower in the utilization of these agricultural chemicals. In addition, very often the efficiency of transport into the ecological system is not as high as desired. The ability to dissolve compounds of this nature in water in high concentrations would represent a significant achievement in this area of use.
With respect to pharmaceutical compounds, water is, of course, the solvent of choice. Indeed, it is normally impossible to use organic solvents as carriers for pharmaceuticals because of the toxicity associated with organic materials or solvents. Moreover, with pharmaceuticals which are used either for oral or injectable dosages, it is desired to have a higher rather than a lower concentration in water, since this decreases the particular amount of the material needed in any given dosage. Often, however, it is extremely difficult to obtain any significant or effective degree of solubility of such compounds in water so as to enhance their pharmaceutical efficacy.
In the past, it has been known that the use of polyvinylpyrrolidone could be used to increase the rate of dissolution of certain organic compounds in water. However, this art does not relate to an increase in solubility, but rather, only to an increase in the rate of dissolution. See L. M. Mortada, "Effect of Polyvinylpyrrolidone and Urea on Dissolution Rate of Phenylbutazone from Solid State Dispersion", Sci. Pharm. 48, 241-247 (1980); 0. I. Corregan, R. F. Timony and M. J. Whelan "The Influence of Polyvinylpyrrolidone on the Dissolution and Bioavailability of Hydrochlorothiazide", J.Phar. Pharmac. 28, 703 (1976); and R. Voight and D. Terborg, "Granulometric Determination of the Effect of PVP on Dissolution Rates of Sparingly Soluble Drugs", Pharmazie, 35, 311-312 (1980).
Numerous methods have been utilized for enhancing the solubility of complicated organic chemicals. For example, in U.S. Pat. No. 3,673,163, a method is described for the use of polyvinylpyrrolidone having molecular weights in excess of 1,000 by coprecipitating the polyvinylpyrrolidone with the drug Acronine. However, the increase in solubility obtained was only about 2.5 times the solubility of the compound. Such an increase in solubility for many of these compounds is not sufficient to render the use of the compound effective from a commercial or practical point of view.
Greater increases in solubility of highly insoluble organic compounds have been obtained as disclosed in application Ser. No. 106,845, filed Oct. 7, 1987, now U.S. Pat. No. 4,853,439. This has been accomplished by complexing the organic compound with a solid homopolymer or copolymer of N-vinyl-2-pyrrolidone having a molecular weight of greater than 1,000. In this method, a coprecipitation technique is used wherein solid N-vinyl-2-pyrrolidone and the organic compound are first dissolved in a mutual organic solvent and the solution is subjected to a complexing reaction. Thereafter, the solvent is removed, leaving the water-soluble complex. However, in certain instances, specific organic compounds do not exhibit as high a water-solubility of the complex as might be desired. Moreover, the method requires several steps, one of which is the removal of the solvent.